Competition between colitogenic Th1 and Th17 cells contributes to the amelioration of colitis
Competition between colitogenic Th1 and Th17 cells contributes to the amelioration of colitis
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DOI：
10.1002/eji.201040379
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发表时间：
2010-09-01
影响因子：
5.4
通讯作者：
Hibi, Toshifumi
中科院分区：
文献类型：
--
作者：
Mikami, Yohei;Kanai, Takanori;Hibi, Toshifumi
Th 17细胞和Th 1细胞协调在炎症性肠病的形成中发挥关键作用。为了研究Th 17和Th 1细胞在炎症部位是如何调节的，我们使用了Th 1-显性CD 4（+）CD 45 RB（高）T细胞转移的RAG-2（-/-）和Th 1/Th 17-混合IL-10（-/-）小鼠。有趣的是，不仅与WT小鼠一起寄生的结肠炎RAG-2（-/-）小鼠显示结肠炎的显著改善，而且在与结肠炎IL-10（-/-）小鼠一起寄生的那些小鼠中也观察到疾病的改善。为了评估Th 1和Th 17致大肠杆菌性T细胞之间的干扰，我们将来自CD 4（+）CD 45 RB（高）T细胞转移的RAG-2（-/-）小鼠和IL-10（-/-）小鼠的固有层（LP）的致大肠杆菌性CD 4（+）T细胞共转移到RAG-2（-/-）小鼠中。令人惊讶的是，共转移的RAG-2（-/-）小鼠显示出与用来自结肠炎RAG-2（-/-）小鼠的细胞单独再转移的RAG-2（-/-）小鼠中所见相似的LP CD 4（+）T细胞的大量细胞浸润，但共转移的RAG-2（-/-）小鼠没有消瘦症状，其在用来自结肠炎IL-10（-/-）小鼠的细胞单独转移的RAG-2（-/-）小鼠中也不存在。此外，与单独转移的配对RAG-2（-/-）小鼠相比，在共转移的小鼠中，源自IL-10（-/-）小鼠的Th 1和Th 17细胞的百分比以及源自结肠炎RAG-2（-/-）小鼠的Th 1细胞的百分比均显著降低，表明Th 1和Th 17细胞处于竞争状态，并且它们的协调导致两种类型的鼠结肠炎的合并的临床表型。
Th17 cells and Th1 cells coordinate to play a critical role in the formation of inflammatory bowel diseases. To examine how Th17 and Th1 cells are regulated at inflammatory sites, we used Th1-dominant CD4(+)CD45RB(high) T cell-transferred RAG-2(-/-) and Th1/Th17-mixed IL-10(-/-) mice. Interestingly, not only did colitic RAG-2(-/-) mice that were parabiosed with WT mice show significant amelioration of colitis, but amelioration of disease was also observed in those parabiosed with colitic IL-10(-/-) mice. To assess the interference between Th1 and Th17 colitogenic T cells, we co-transferred colitogenic CD4(+) T cells from the lamina propria (LP) of CD4(+)CD45RB(high) T cell-transferred RAG-2(-/-) mice and IL-10(-/-) mice into RAG-2(-/-) mice. Surprisingly, the co-transferred RAG-2(-/-) mice showed a vast cellular infiltration of LP CD4(+) T cells similar to that seen in RAG-2(-/-) mice re-transferred with the cells from colitic RAG-2(-/-) mice alone, but the co-transferred RAG-2(-/-) mice did not have the wasting symptoms, which are also absent in RAG-2(-/-) mice transferred with cells from colitic IL-10(-/-) mice alone. Furthermore, the percentages of Th1 and Th17 cells originating from IL-10(-/-) mice and those of Th1 cells originating from colitic RAG-2(-/-) mice were all significantly decreased in the co-transferred mice as compared with the singly-transferred paired RAG-2(-/-) mice, suggesting that Th1 and Th17 cells are in competition, and that their orchestration results in a merged clinical phenotype of the two types of murine colitis.